MOLECULAR MECHANISMS OF THE PROTO-ONCOGENE BCL6 IN GLIOBLASTOMA

Abstract

ZBTB TRANSCRIPTION FACTORS ORCHESTRATE GENE EXPRESSION DURING HUMAN DEVELOPMENT. HOWEVER, THEIR ROLES IN GLIOBLASTOMA MULTIFORME (GBM) REMAIN LARGELY UNEXPLORED. HERE I IDENTIFY BCL6, AN ONCOGENIC PROTEIN IN LYMPHOMA, AS AN IMPORTANT GLIOMA-PROMOTING FACTOR. BCL6 EXPRESSION IS ELEVATED IN AND NECESSARY FOR THE GROWTH OF GBM. BCL6 MODULATES THE EXPRESSION OF TP53, AXL AND MET. THE ACTIVATED BCL6-AXL SIGNALS THROUGH MEK-ERK AND S6K-RPS6 AXES, AND PROMOTES CAP-DEPENDENT TRANSLATION. MOREOVER, DEPLETION OF BCL6 OR PHARMACOLOGICAL INHIBITION OF BCL6/NCOR COMPLEX EFFECTIVELY BLOCKS GBM GROWTH. TOGETHER, THESE FINDINGS UNCOVER A NOVEL GROWTH PROMOTING ROLE OF BCL6 IN GBM, AND PROVIDE THE RATIONALE AND EVIDENCE TO TARGET THIS PROTEIN IN GBM TREATMENT.